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PSYCHOPHARMACOLOGY UNDERGRADUATE COURSE

PSYCHOPHARMACOLOGY UNDERGRADUATE COURSE. ABDULLAH AL-SUBAIE, MBBS, FRCP (C) PROFESSOR OF PSYCHIATRY Twitter: @ prof_subaie. DRUGS IN PSYCHIATRY PSYCHOACTIVE DRUGS. ANTIPSYCHTIC DRUGS ANTIDEPRESSANT DRUGS MOOD STABILIZING DRUGS ANTIANXIETY DRUGS ELECTROCONVULSIVE THERAPY (ECT).

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PSYCHOPHARMACOLOGY UNDERGRADUATE COURSE

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  1. PSYCHOPHARMACOLOGYUNDERGRADUATE COURSE ABDULLAH AL-SUBAIE, MBBS, FRCP (C) PROFESSOR OF PSYCHIATRY Twitter: @prof_subaie Psychopharma/ Prof.Subaie

  2. DRUGS IN PSYCHIATRYPSYCHOACTIVE DRUGS • ANTIPSYCHTIC DRUGS • ANTIDEPRESSANT DRUGS • MOOD STABILIZING DRUGS • ANTIANXIETY DRUGS • ELECTROCONVULSIVE THERAPY (ECT) Psychopharma/ Prof.Subaie

  3. ANTIPSYCHOTIC DRUGSNEUROLEPTICS / MAJOR TRANQUILIZERS • Treat all psychoses & psychotic symptoms e.g. in autism, organic brain syndrome... • Block D2 receptors in the mesolimbic system • Not addictive Psychopharma/ Prof.Subaie

  4. Olanzepine (10-30mg) Risperidone (4-12mg) Clozepine (100-800mg) Sulpride (200-800mg) Amisulpride (200-800mg) Haloperidole (5-100mg) Aliphatic e.g. Chlorpromazine (300-1500mg) Pipiridine e.g. Thioridazine (300-800mg) Piperazine Loxapine (25-100mg) Alipathic e.g. Chlorprothexine (75-600mg) Piperazine e.g. Thiothexine (5-60mg) Fluanoxol (3-10 mg) Molindone (50-250mg) Pimozide (2-12 mg) Psychopharma/ Prof.Subaie

  5. ANTIPSYCHOTIC DRUGSNEUROLEPTICS / MAJOR TRANQUILIZERS Mechanism of action • In typical antipsychotics • Blockage of D2 – receptors in: • Nigro-strial (psychiatric tract) • Substantia Nigra (Neurological tract) • Tubero-infundibular tract (Endocrine tract) • In atypical antipsychotics: • Blockage of 5HT2A/D2 receptors Psychopharma/ Prof.Subaie

  6. ANTIPSYCHOTIC DRUGSNEUROLEPTICS / MAJOR TRANQUILIZERS Meso-limbic (Psychiaitrc tract) Nigro-strial (Neurologic tract) Meso-cortical (Psychiatric tract) Tubero-infundibular (Endocrine tract) Psychopharma/ Prof.Subaie

  7. ANTIPSYCHOTIC DRUGSSide effects (hint) • High Potency typical antipsychotics: Neurological side effects • Low Potency typical antipsychotics: other side effects Psychopharma/ Prof.Subaie

  8. Due to D2 blockade Parkinsonian syndrome ANTIPSYCHOTIC DRUGSNeurologic Side effects How to manage? Position & gait Apathy Drooling Fine tremor Staring eyes Psychopharma/ Prof.Subaie

  9. Due to D2 blockade Parkinsonian syndrome Akathesia (Motor restlessness) ANTIPSYCHOTIC DRUGSNeurologic Side effects D.Dx How to manage? Subjective feelings of restlessness Objective signs of restlessness Feelings of anxiety, inability to relax, jitteriness, pacing, rocking motions while sitting, rapid alterations of position. More in middle aged women Psychopharma/ Prof.Subaie

  10. Due to D2 blockade Parkinsonian syndrome Akathesia (Motor restlessness) Acute dystonia ANTIPSYCHOTIC DRUGSNeurologic Side effects How to manage? Brief or prolonged muscle contraction leading to abnormal movements or postures e.g. Occulogyric crises, tongue protrusion, torticollis, laryngeal pharyngeal dystonias and dystonic Postures - Early onset, more in young men and high doses of typical neurosleptics Psychopharma/ Prof.Subaie

  11. Due to D2 blockade Parkinsonian syndrome Akathesia (Motor restlessness) Acute dystonia Tardive Dykinesia ANTIPSYCHOTIC DRUGSNeurologic Side effects Why? How to manage? Involuntary choreiform, athetoid or rhythmic movements of the tongue, jaw, trunk or extremities More with long term typical neuroleptic treatment, old age, female sex, mood disorder, cognitive disorders. Psychopharma/ Prof.Subaie

  12. Due to D2 blockade Parkinsonian syndrome Akathesia (Motor restlessness) Acute dystonia Tardive Dyskinesia Neuroleptic malignant syndrome ANTIPSYCHOTIC DRUGSNeurologic Side effects How to manage? Muscular rigidity, akinesia, mutism, obtundation & agitation, hyper-thermia, swaeting, tachycardia, Hypertension. Increased wBC, incraesed CPK, liver enzymes, and plasma myoglobulin. Myoglobulinuria, may occur and may lead to renal failure. Symptoms evolve in 1-3 days & may last 10-14 days. May occur at any time More common in young men Mortality: 20% - 30%( higher with depot) Psychopharma/ Prof.Subaie

  13. Muscarenic (anti-cholenergic): dry mouth Constipation Blurred vision, urinary retention Precipitation of narow angle glucoma Alpha–1–adrenergic blockade: Orthostatic hypotension Impotence Impaired ejaculation ANTIPSYCHOTIC DRUGSOther Side effects Psychopharma/ Prof.Subaie

  14. CNS Side effects: Sedation Metabolic / Endocrine Side effects: weight gain Increased BS & lipids Galactorrhea Amenorrhea Allergic Side effects Cholestatic jaundice Agranulostasis Cardiac side effects: EKG changes Arrythmias Occular Side effects: Corneal Opacities Retinitis pigmentoza Dermatological Side effects: Photosensitivities Metallic discoloration Contact dermatitis ANTIPSYCHOTIC DRUGSOther Side effects Psychopharma/ Prof.Subaie

  15. ANTIDEPRESSANTS • Treat: Major depression, dysthymic disorder, nocturnal enuresis, chronic pain, panic disorder, OCD, ADHD, school phobia, other phobias, generalized anxiety disorder, insomnia… • Work through: Serotonin, Norepinephrine, Dopamine • Not addictive Psychopharma/ Prof.Subaie

  16. ANTIDEPRESSANTS Imipramine, Amitriptyline, Chlomipramine (150–300mg) Moclobemide (300– 600 mg) Flouxetine, Paroxetine, citalopram (20-80mg) Venlafaxine (75-300mg), Mertazepine 30-60mg) Phenelzine (15-60mg), Tranycypramine (10-30mg) Psychopharma/ Prof.Subaie

  17. ANTIDEPRESSANTSMechanism of action Inhibition of reuptake Inhibition of mono-amaine oxidaze enzyme Inhibition of auto-receptors Down regulation of beta-adrenergic post-synaptic receptors Psychopharma/ Prof.Subaie

  18. HETEROCYCLICS: Muscarenic (anti-cholenergic): dry mouth Constipation Blurred vision, urinary retention Precipitation of narow angle glucoma Alpha–1–adrenergic blockade: Orthostatic hypotension Impotence Impaired ejaculation ANTIDEPRESSANT DRUGSSide effects Psychopharma/ Prof.Subaie

  19. Delirium Coma seizures Agitation Hallucinations Severe hypotension Supra-ventricular tachycardia Flushing Mydriasis Dry skin Hyperthermia Decreased bowel sounds. ANTIDEPRESSANT DRUGSSide effects Management • Stop HCA immediately • Physostigmine (anticholinesterase inhibitor) 1-2 mg IV or IM every 20 – 60 minutes, until improvement occurs • Cardiac monitoring and life support (physostigmine may lead to severe BP drop and bronchial constriction) • Benzodiazepines may be used. Central anti-cholenergic syndrome: Psychopharma/ Prof.Subaie

  20. ANTIDEPRESSANTSSide effects • HETEROCYCLICS: • SSRI: • have a much better side effect profile: • Agitation • Sexual problems • Stomach upset • Hypersomnia/insomnia Psychopharma/ Prof.Subaie

  21. ANTIDEPRESSANTSSide effects • HETEROCYCLICS: • SSRIs • MAOI: • Hypertensive crisis (tyramine reaction) Nifedipine (guard, against rapid BP drop) (patient bites the capsule and swallows its contents in water) Phentolamine (alpha-adrenergic antagonist) Chlorpromazine (alpha-adrenergic Antagonist) Psychopharma/ Prof.Subaie

  22. ANTIDEPRESSANTSSide effects • HETEROCYCLICS: • SSRI: • MAOI: • Cardiovascular (orthostatic hypotension, tyramine hypertensive crisis) • Sexual (Impotence & delayed ejaculation) • Neurologic (insomnia, seizure& euphoria) • Hepatic: (Cholestatic reaction). Psychopharma/ Prof.Subaie

  23. ANTIDEPRESSANTSSide effects • HETEROCYCLICS: • SSRI: • MAOI: • Interaction: • Diet: Amphetamines Decongestants & nasal sprays (Ephedrine….) Epinephrine (local anesthesia) Aldomet Aged cheese Pickled herriag Raisin Alcohol Chicken liver Beans Figs Yeast products Chocolate Psychopharma/ Prof.Subaie

  24. TREATING DEPRESSION • Confirm diagnosis • Rule out contraindications • Make use of side effects • Start with a small dose and build it up • Side effects start sooner but therapeutic effects start only 2-3weeks later • When patient improves, maintain treatment for 9 months, then cut down gradually watching for re-emergence of symptoms Psychopharma/ Prof.Subaie

  25. TREATING DEPRESSION SUICIDE Psychopharma/ Prof.Subaie

  26. MOOD STABLIZERS • Lithium Carbonate • Sodium Valproate • Carbamazepine • Lamotrigine • Topiramate • Clozapine Psychopharma/ Prof.Subaie

  27. MOOD STABLIZERSIndications • Acute mania • Prophylaxis against both mania and depression • Schizoaffective disorder. • Impulse control disorder Psychopharma/ Prof.Subaie

  28. LITHIUM CARBONATE • PHARMACOLOGY • Rapidly absorbed • Peaks in 30-60 minutes • Completely absored in 8 hours • Water soluble, not protein bound • Steady state is reached in 7 days. • Excreted though the kidneys, not metabolized. • MECHANISM OF ACTION • Unknown exactly • ? stabilizes cell membranes Psychopharma/ Prof.Subaie

  29. LITHIUM CARBONATEAdministration • Assess the kidney functions, thyroid functions, cardiac and CNS condition. • After starting treatment, periodically assess drug level and kidney & thyroid functions. • Aim at a blood level of of: 0.8 – 1.2 mEq/l (acute mania), 0.6 – 0.8 mEq/l (prophylaxis) (12 hours after the last dose) Psychopharma/ Prof.Subaie

  30. LITHIUM CARBONATESide effects • Neurological: Tremor (50%), weakness, cog-wheeling • Renal: Occur in 10-50 % e.g. polyuria, polydipsia, nephrogenic D.I., nephrotic syndrome, (tubular changes with chronic use and high levels) • Cardiac: Similar to those of hypokalimia e.g. U-wave and T-wave depression • Endocrine: Goiter, hypothyroidism, abnormal thyroid functions (30-40%) • Dermatological: Acne, exacerbation of psoriasis ), hair loss. • Pregnancy and lactation: Teratogenicity (level in milk=30-100% of maternal blood level) • Toxicity: (seizures, delirium, cerebellar signs, coma) occurs in blood level= 1.2 – 2 mEq/l. Lethal levels above that. Psychopharma/ Prof.Subaie

  31. CARBAMAZPINE • PHARMACOLOGY • Absorbed slowly from the G.I. tract • Peaks in plasma in 2-8 hours and steady state level is reached in 2-4 days • Induces liver enzymes • MECHANIZM OF ACTION • UNCLEAR: increase of hippocampal GABA receptor density Psychopharma/ Prof.Subaie

  32. CARBAMAZEPINEAdministration • Assess blood count and liver functions • Start with a small dose and use clinical condition & drug level as a guide • Assess liver functions, blood level and blood count periodically. • Aim at a blood level of 6-12 mg/l after 10-12 hours of last dose (12 hours after the last dose) Psychopharma/ Prof.Subaie

  33. CARBAMAZEPINESide effects • CNS: drowsiness and in diplopia, dizziness, nausea, vomiting and ataxia(toxic doses) • Dermatological: skin rash, Steven–Johnson Syndrome, photosensitivity. • Hepatic: cholestatic jaundice. • Hematological: Leuckopenia, thrombocytopenic purpura, and bone marrow suppression. Psychopharma/ Prof.Subaie

  34. CARBMAZEPINEContra-indications • A-V heart block • Liver disease • Leuckopenia • Cerebellar lesions • Co-administration with Clozapine Psychopharma/ Prof.Subaie

  35. SODIUM VALPROATE • PHARMACOLOGY • Completely absorbed from the stomach • Peaks in plasma in 1-2 hours • Metabolized by liver • MECHANIZM OF ACTION • UNCLEAR: increase of hippocampal GABA receptor density Psychopharma/ Prof.Subaie

  36. SODIUM VALPROATEAdministration • Assess liver functions • Start with a small dose and use clinical condition & drug level as a guide. • Assess liver functions and blood level periodically. • Aim at a blood level of 50-120 mg/l after 10-12 hours of last dose (12 hours after the last dose) Psychopharma/ Prof.Subaie

  37. SODIUM VALPROATESide effects • Nausea & vomiting. • Impairment of liver enzymes • Liver toxicity (in toxic doses) • Hair loss • Weight gain • Sedation, ataxia and dyarthria • Ovarian cysts in young females ? Psychopharma/ Prof.Subaie

  38. SODIUM VALPROATEContra-indications • Liver disease. • Co-administration with hepato-toxic drugs such as pemoline. • Thrombocytopenia and platelet dysfunction Psychopharma/ Prof.Subaie

  39. ANTI-ANXIETY DRUGS • Barbiturates • Benzodiazepines • Non-benzodiazepines, non-barbiturates: e.g. TCAs and antihistamine • Buspirone • SSRIs • Antipsychotics Psychopharma/ Prof.Subaie

  40. BENZODIAZEPINES • CLASSIFICATION: • Very short acting e. g. Triazolam • Short acting: e. g. Oxazepam, Lorazepam, Alprazolam • Long acting : e.g. Diazepam, Chlordiazepoxide • PHARMACOLOGY: • Completely absorbed from the G.I. tract • Rapid action due to high lipid solubility • Peaks in plasma in 1-3 hours. • Metabolized in the liver • MECHANIZM OF ACTION: • Through its own receptors • Through increased affinity for GABA receptors Psychopharma/ Prof.Subaie

  41. BENZODIAZEPINESSide-effects • Sedation • Dizziness and ataxia • CNS depression when used with sedative substances or alcohol • Disinhibition and aggression • Tolerance and withdrawal (dependence) Psychopharma/ Prof.Subaie

  42. BENZODIAZEPINESIndications • Insomnia • Anxiety Symptoms • Panic Disorder • Social phobia and other phobias • Mania • Akathesia • Alcohol Withdrawal Psychopharma/ Prof.Subaie

  43. BENZODIAZEPINESContra-indications • Potential abuse • Compromised cardiovascular system functions • Caution in elderly • Driving & operating heavy machines Psychopharma/ Prof.Subaie

  44. BUSPIRONE • PHARMACOLOGY: • Well absorbed from the G.I. tract • Metabolized by the liver • Peaks in plasma in 1-1.5 hours • MECHANISM OF ACTION: • Unlike benzodiazepines it has no effect on GABA neurotransmitter • It is an agonist of 5HT-1-A, reduces firing of the serotonegic neurones in the median raphe nuclei Psychopharma/ Prof.Subaie

  45. BUSPIRONEAdministration • Well tolerated & safe • Takes long time to work • Does not lead to dependence Psychopharma/ Prof.Subaie

  46. Visit our website: www.alnafsy.com Psychopharma/ Prof.Subaie

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